tbuckley/cabot-search huggingface dataset:
Trial in progress: A phase II, multicenter, open-label study of PolyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301).
Authors: Joleen M. Hubbard, Daniel H. Ahn, Jeremy Clifton Jones, Kathleen Wittenberger, Levente Molnar, Orsolya Lorincz, Eszter Somogyi, Zsolt Csiszovszki, Hagop Youssoufian, Eniko Rita Toke
Journal: Journal of Clinical Oncology (2023)

TPS283 Background: Colorectal cancer (CRC) is among the top three most commonly occurring cancers globally. CRC is now routinely classified as MSI-high (MSI-H) or microsatellite-stable (MSS) based on the detection or absence of molecular markers of genetic instability, respectively. The efficacy of checkpoint inhibitor immunotherapy in MSI-H CRC has not been replicated in MSS CRC. Therefore, additional interventions are needed to convert immunologically “cold” MSS CRC to “hot” tumors resembling MSI-H tumors. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine containing 12 immunogenic epitopes derived from 7 cancer testis antigens (CTAs) frequently expressed in patients with CRC. PolyPEPI1018 successfully restored and boosted pre-existing anticancer immunity of MSS mCRC subjects and triggered recruitment and infiltration of cytotoxic T cells into the tumor. In first line metastatic MSS CRC, PolyPEPI1018 in combination with fluoropyrimidine/bevacizumab vaccine was safe and demonstrated early evidence of clinical activity. Therefore, we hypothesized that the combination of PolyPEPI1018 and atezolizumab will convert a “cold” MSS mCRC to a “hot” tumor and may increase the likelihood of inducing favorable antitumor immunity and subsequent clinical benefit. Methods: The study is a phase 2, multicenter, single-arm clinical trial of PolyPEPI1018 vaccine (1.2 mg, sc, every 3 weeks) and atezolizumab (1200 mg, iv, every 3 weeks) for patients with advanced or metastatic MSS CRC who have progressed on 2 or 3 lines of prior standard regimens. 28 patients will be enrolled at 3 US sites with a primary objective to assess the safety and tolerability of multiple doses of PolyPEPI1018 in combination with atezolizumab. Secondary endpoints include objective response rate (ORR) assessed by RECIST v1.1, vaccine induced immunological response rate (IRR), progression-free survival and overall survival. Correlative aims include assessing blood and tissue biomarkers (PD-L1, Immunoscore ® IC, ctDNA, clinical tumor markers) for association with clinical benefit. An exploratory study is being conducted for co-development of a companion diagnostic based on HLA-genotype and computational personal epitope (PEPI) prediction test. A Simon 2-stage design will be used for the initial assessment of ORR. If pre-specified activity goal for the first stage of accrual (n = 18) is met, additional 10 participants will be enrolled to the second stage. A formal review of safety will be performed after the initial 6 participants have received at least 2 cycles of study therapy. The study is open with 10 patients enrolled at time of submission. Clinical trial information: NCT05243862 .
Safety of ramucirumab in patients with advanced gastric cancer in Europe and North America: A prospective observational registry.
Authors: Lucrezia Silvestro, Ferdinando De Vita, Arndt Vogel, Thomas Jens Ettrich, Eric Van Cutsem, Maria Di Bartolomeo, Yulia D'yachkova, Astra M. Liepa, Natalia Smolyakova, Mariusz Lukanowski, Yu-Jing Huang
Journal: Journal of Clinical Oncology (2023)

341 Background: The objective was to describe the safety of ramucirumab (Ram) for previously treated advanced gastric cancer under real-world conditions in Europe and North America. Methods: This was a non-interventional, descriptive study of adult patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed after first-line chemotherapy (I4T-MC-JVDD). Data collection began in December 2015 and was completed in August 2021. Patients were followed up to 12 months after initiation of Ram. Safety outcomes included adverse events (AEs)/serious AEs (SAEs), and AEs leading to dose adjustment or death. Subgroups of interest were elderly, patients with cardiac comorbidities, hepatic, or renal impairment. Results: 606 patients were classified in 3 cohorts: Ram monotherapy (Ram Mono, N=51); Ram plus paclitaxel (Ram+PTX, N=547); or Ram plus other anti-cancer agents (N=8). Most patients were male (70%), white (97%) and aged ≥65 (55%); 22% of the population was ≥75 years old. Metastatic cancer was reported in 552 patients (96%); primary tumor location was gastric in 417 patients (69%) and in the gastroesophageal junction in 189 patients (31%). Patients were previously treated mainly with platinum (97%) and fluoropyrimidine (96%). Hypertension was the most frequently reported historical medical condition (25%). At baseline, 23% patients had documented cardiac comorbidities, 11% hepatic impairment and 6% renal impairment. The median duration of Ram was 8 weeks (IQR=4.0-10.6) in Ram Mono and 15 weeks (IQR=8.4-26.7) in Ram+PTX. Regardless of causality, 98% of patients experienced ≥1 AE; most commonly fatigue (31%) and abdominal pain (20%) in Ram Mono cohort; and fatigue (46%) and neuropathy (31%) in Ram+PTX cohort. In total, 40% experienced ≥1 AE of special interest; most commonly bleeding/hemorrhage (21% [mainly epistaxis]) and hypertension (11%). In total, 33 patients (5%) died due to AEs that occurred on, or within 90 days of last dose of Ram, 9 (2%) were related to Ram treatment as per physician’s assessment. Conclusions: The observed safety profile of Ram in the real-world setting was manageable and consistent with the established safety profile of Ram identified from clinical trials. No new safety concerns or notable findings were observed overall or in the subgroups of interest. Clinical trial information: ENCEPP/SDPP/9400 . [Table: see text]
Prognostic impact of immune-related adverse events on survival outcomes in metastatic gastrointestinal cancer: A single-institutional experience.
Authors: Olisaemeka Ogbue, Serhan Unlu, Sharmeen Sorathia, Abdel Rahman Nanah, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2023)

801 Background: Immune checkpoint inhibitors (ICIs) have several approved indications in the treatment of gastrointestinal (GI) malignancies including metastatic disease. The adverse events related to ICI use or Immune related adverse events (irAEs) are now being more readily recognized. The association between the occurrence of irAEs and survival outcomes is not well understood. Whereas complete tolerability of ICIs with minimal irAEs may be indicative of a lack of response, the development of moderate to severe irAEs could result in significant morbidity and mortality especially in already advanced disease. This dilemma has provided an impetus to present our 5-year single institutional experience wherein we aim to determine the impact of irAEs on survival outcomes in metastatic GI malignancies. Methods: We retrospectively reviewed a cohort of adult patients who received ICIs for metastatic GI malignancies at the Cleveland Clinic foundation between 2017-2022 by utilizing an outpatient oncology pharmacy database. ICIs of interest included atezolizumab, ipilimumab, nivolumab and pembrolizumab. The occurrence of irAEs was as determined by primary oncologist. The primary and secondary outcomes were overall survival (OS) and progression free survival (PFS) in patients based on irAE presence, respectively. Results: There was a total of 151 patients who received ICIs for various metastatic GI malignancies. Among these, 38 unique irAEs were identified constituting 25% of the entire cohort. The table shows their distribution by organ system and type of GI malignancy. We observed hyper progressive disease in 3% of irAE cohort. Grade 3-4 irAEs requiring hospitalization occurred in 32% of all irAEs, median hospital length of stay of 5 (range:1-15) days with 11% resulting in death. 26 % discontinued treatment due to irAEs while 44% had palliative care consultations/hospice transition soon after. The median OS rates in patients who had irAEs vs those who didn’t, respectively, were 10 months [95% confidence interval (CI, 5-NA)] vs. 9 months [95% confidence interval (CI, 6-12)], p=0.85. There was also no statistically significant difference in median PFS between both groups (p=0.76). Conclusions: In our single institution cohort of metastatic gastrointestinal cancer patients, despite significant morbidity from irAEs, the prognosis was similar as previous studies suggesting a better outcome in patients with irAEs compared to those who did not experience irAEs.[Table: see text]
Tislelizumab in combination with anlotinib as first-line treatment for unresectable hepatocellular carcinoma: A single-arm, phase II clinical trial.
Authors: Shi-xue Laoguo, Huasheng Huang, Jie Zeng, Yangfeng Jiang, Cuizhen Liu, Ning Mo, GuangZhi Zhu, Fuchao Ma, Tao Peng, Zhiming Zeng, Jie Ma
Journal: Journal of Clinical Oncology (2023)

576 Background: The inability to perform liver resection is an important cause of high mortality in Hepatocellular carcinoma (HCC) patients. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitor) and tislelizumab (anti‐PD‐1 antibody) in HCC pts, we therefore evaluated the safety and efficacy of tislelizumab plus anlotinib as first-line therapy for patients with unresectable HCC. Methods: Patients aged 18-75 years, with unresectable HCC, ECOG PS 0-3, BCLC stage A-D, Child-Pugh score A-C, and CNLC stage Ia-IV were enrolled. Patients who met the inclusion criteria received tislelizumab(intravenous drip, 200 mg/d1, Q3W) and anlotinib(oral, 8-12 mg/d1-14, Q3W). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR),overall survival (OS), progression-free survival (PFS), adverse events (AEs), and serious adverse events (SAEs). Results: Between Sep-2020 until Sep-2022, 37 patients were enrolled, and 25 patients’ clinical data were available to assess clinical efficacy. The median age of the pts was 62 years (ranged 31-72 years), 15 pts (60%) ECOG PS 1, 14 pts (56%) BCLC stage C, 17 pts (68%) Hepatitis B Virus Infection and 13 pts (52%) had received prior local regional therapy. The ORR per mRECIST was 32% (95% CI, 12.3%-51.7%) and DCR was 72% (95% CI, 53.1%-90.9%). The best clinical response was CR in 2 pts (8%), 6 pts (24%) PR and 10 pts (40%) SD. With a median follow-up of 12.7 months, the estimated median PFS was 11.8 months, and the median OS was not reached. The most common AEs during follow-up were AST increased (52%), γ-GT increased (48%), and hypoalbuminemia (48%). Conclusions: Tislelizumab combined with anlotinib showed high antitumor activity and good tolerability in the treatment of unresectable HCC, which may be an effective and safe treatment option.
The inequity in emergency room utilization prior to colorectal cancer diagnosis and the opportunity to improve access to colorectal cancer screening.
Authors: Afsaneh Barzi, Juanjuan Zhang, Lihua Liu, Sue Kim
Journal: Journal of Clinical Oncology (2023)

79 Background: The opportunity for early detection of colorectal cancer via screening is not fully realized. Previous efforts to maximize use of screening had targeted patients and primary care providers. Other wildly used healthcare settings may be suitable targets for intervention. We explored emergency room (ER) utilization in patients with colorectal cancer prior to their diagnosis using the linkage between California Cancer Registry (CCR) and OSHPD (Office of Statewide Health Planning and Development). Methods: Patients with diagnosis of colorectal cancer 2010-2015 were identified in the CCR and their records were linked with OSHPD (2009 – 2016) to assess ER utilization. This study aimed to evaluate the patterns of ER utilization (all and nay reason for ER visit) prior to the diagnosis of colorectal cancer. Results: A total of 66,451 colorectal cancer patients were identified, of which 57,876 (87%) were linked with OSHPD data. Among the linked population, 41% (23,890) had at least one ER visit prior to their diagnosis of colon cancer. Of the 23,890 with ER visit, 14% had 3 or more ER visits. The median number of days from first ER visit to diagnosis was 539 days (range: 2551 – 1). A total of 14,372 patients (25%) had an ER visit within one year of their colorectal cancer diagnosis. The median age of patients who had ER visits was younger than those who didn’t have an ER visit, 66 vs. 68 years. There was no difference in the number of ER visits between patients 50 and younger and those older than 50 years. There was no significant difference in the stage at presentation between those with prior ER visit and those without. Patients in high socioeconomic status were less likely to have an ER visit prior to colorectal cancer diagnosis (44%) compared to those with low SES status (36%). Patients with private insurance had a significantly lower likelihood of ER visits compared to those with federal and state funded insurance. Conclusions: A significant percentage of patients with colorectal cancer had ER visit prior to their diagnosis, many within one year of their diagnosis. Inequity in access to care, measured via poor SES and insurance type, was associated with higher chance of ER visit among colorectal cancer patients. Emergency room may be a targetable opportunity to remind and coordinate screening for colorectal cancer.
Safety and efficacy of prophylactic pegfilgrastim on day 3 of neoadjuvant DCF chemotherapy in elderly patients with resectable esophageal cancer.
Authors: Go Ikeda, Yuri Yoshinami, Toru Kadono, Toshiharu Hirose, Akihiro Ohara, Mai Itoyama, Ikuko Azuma, Shun Yamamoto, Yoshitaka Honma, Koshiro Ishiyama, Jyunya Oguma, Hiroyuki Daiko, Ken Kato
Journal: Journal of Clinical Oncology (2023)

375 Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m 2 , CDDP [day 1]: 70 mg/m 2 , 5-FU [continuous infusion on days 1-5]: 750 mg/m 2 , every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.
Diagnostics and treatment for HER2+ mG&amp;CRC: Learning outcomes of GetSMART.
Authors: Emil Lou, John Marshall, Ginny Jacobs, Matthew Fleming, Anelisa Kruschewsky Coutinho, Takayuki Yoshino, Monica Augustyniak, Pam McFadden
Journal: Journal of Clinical Oncology (2023)

82 Background: Gastric/colorectal cancer (G&amp;CRC) are among the most prevalent cancers. Efforts are ongoing to better assess their clinical/genomic factors. HER2 (human epidermal growth factor receptor 2) testing is strongly recommended in clinical practice to guide treatment. An accredited education program (GetSMART) was launched online (January 2021–April 2022) to equip healthcare providers (HCPs) with knowledge, skills, and confidence to accurately assess/apply molecular testing and therapy options for metastatic G&amp;CRC patients. Methods: A knowledge/confidence-based assessment was embedded in four modules to measure learners’ knowledge mastery (% answering correctly with confidence) pre/post-activity. Self-reported confidence and anticipated performance in clinical practice were measured before/after each module. At the end of program, HCPs were asked about their commitment to change. McNemar’s test was applied to assess statistical significance in pre-post for paired items, and descriptive analysis for non-paired items. Results: Overall, 925 unique HCPs engaged in GetSMART, 31% (n=284) completed all modules, of which 57% (n=163) consented analysis of their data. A statistically significant increase (p&lt;0.05) was measured in percentage of HCPs demonstrating knowledge mastery, confidence, and commitment to change their practice from pre to post across four competencies, except for percentage of HCPs “often”/“always” engaging patients in shared decision-making (SDM) (3, Performance). Largest gains in knowledge mastery/confidence were noted for HCPs’ ability to anticipate/manage adverse events (AE) ( 4A); and for anticipated performance, in HCPs considering appropriate treatment. Post-activity, 66% (98/149) of HCPs intended to change practice based on module content, 83% (70/84) of whom were “highly”/“somewhat” confident to make changes. The activity’s anticipated impact on patients was rated “major”/“moderate” by 69% (103/149) of HCPs. Conclusions: Identification of HER2 aberrations in mG&amp;CRC and its appropriate treatment selection remains challenging in oncology care. This evaluation demonstrated that GetSMART positively impacted HCPs’ knowledge, confidence, and anticipated performance in clinical practice to enhance health outcomes of HER2+ mG&amp;CRC patients. [Table: see text]
Overall survival in patients with metastatic or locally advanced pancreatic cancer following chemoradiation with novel combination of aldoxorubicin, N-803 IL-15 superagonist, and PDL1- NK cell therapy.
Authors: Tara Elisabeth Seery, Chaitali Singh Nangia, Phillip D. Reid, Bruno Fang, Heidi Ann McKean, Leonard S. Sender, Sandeep K. Reddy, Patrick Soon-Shiong
Journal: Journal of Clinical Oncology (2023)

720 Background: Pancreatic cancer claimed an estimated 47,050 lives in the USA in 2020, with an expected median overall survival (OS) of 3 months in 3rd line. (Manax ASCO GI 2019), with no evidence of disease control in these late stage patients. We hypothesize that effective response against pancreatic cancer requires orchestration of both the innate and adaptive immune system to accomplish immunogenic cell death with survival benefit. Herein we report updated results of the fully enrolled cohort of a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine superagonist ), and allogeneic off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: We report data from a multi-center study, on 83 3rd line or greater, subjects treated with low dose, chemo radiation Nab-paclitaxel (100 mg/ m2 IV), Gemcitabine (600 mg/m2 IV); Cyclophosphamide (50 mg PO BID) and low dose SBRT. This induction immuno-modulation therapy to induce DAMPs was followed with investigational agents activating the innate and adaptive systems: Aldoxorubicin (150 mg/m2 IV), N-803, an IL-15 superagonist (15 μg/kg SC) and PD-L1 t-haNK (~2 × 109cells/dose IV). Prophylactic G-CSF or EPO was not allowed. All treatments were administered on an outpatient basis. Results: As of submission, median follow-up is 4.9 months. Median age 62, M:F ratio 46:36. ECOG 0-1,97%. 74/83 (89%) reported at least 1 investigational product related AE (TRAE) with 63/83 (76%) reporting at least 1 TRA grade 3 or higher. The most common were anemia 41%, neutropenia 20%, thrombocytopenia 10%, all others &lt;10%. SAEs attributed to investigational agents were reported in 8/83 (10%) patients. Treatment is ongoing for 6 subjects (7%), with 17.1 months as the longest duration on therapy to date. Median OS is 5.7 months (95% CI: 4.9, 6.4) with 26/83 alive to date. Median PFS is 2.3 months (95% CI: 2.0, 3.6) and 37% of subjects achieving stable disease &gt;=8 weeks. Median OS in 3 rd line (N=38) is 6.3 months, Median OS in 4 th line or greater (N=40) is 5.0 months. Conclusions: Historical 3 month median OS in 3 rd line metastatic pancreatic cancer patients has been exceeded. A doubling of survival in 3 rd line is seen in QUILT 88 investigating a novel combination immunotherapy protocol of low-dose chemoradiation, N-803 and PDL1 t-haNK therapy. Updated data will be presented. Clinical trial information: NCT03563144 .
Real-world survival of patients (pts) with colorectal adenocarcinoma liver metastases (CRLM) treated with transarterial radioembolization (TARE).
Authors: Sharmeen Mahmood, Garo Greg Hagopian, Ben Sadeghi, Jeffrey V Kuo, David Imagawa, Dayantha Fernando, Nadine Abi-Jaoudeh, Farshid Dayyani
Journal: Journal of Clinical Oncology (2023)

40 Background: While TARE with yttrium-90 (Y90) microspheres can induce tumor responses and improve progression-free survival (PFS) in pts with CRLM, randomized trials have not shown an overall survival (OS) benefit. It is unclear whether this is due to suboptimal pt selection and/or trial design vs. possibly a radiation-induced delayed liver damage which compromises OS. The objective was to describe real world OS with TARE for pts evaluated at an academic center (University of California Irvine) with a dedicated multidisciplinary liver tumor board (MTB). Methods: Retrospective study of consecutive pts with CRLM undergoing TARE between 01/2016-07/2020. We performed descriptive analyses for relevant pt and tumor characteristics, Wilcoxon Signed-Rank Test for comparison of continuous variables, and Kaplan-Meier estimates for survival. Results: N=55 pts were included. Follow-up time was at least 24 mo. Median age was 60 yrs (range 36-84), 61.8% were female, Caucasian/Hispanic/Asian/Other= 54.4%/16.4%16.4%/12.7%, ECOG 0/1/2= 32.7%/58.2%/9.1%, tumor sidedness: left/right/unknown 72.7%/23.6%/3.6%, number or prior lines of systemic treatment 1/2/3+= 38.2%/26.4%/21.8%. MSI-High= 3.6% and RAS/RAF mutations were present/absent/unknown in 34.5%/49.1%/16.4%. Baseline and post-TARE liver function tests are shown in the table. Median time from diagnosis to first TARE was 16.4 mo (1.7-95.6) and 36.4% were treated within the first 12 mo of diagnosis. Median OS from diagnosis and first TARE were 43.2 mo (29.5-68.7) and 16.7 mo (9.9-35.2), respectively. Conclusions: The observed OS of pts with CRLM treated with TARE with a mature follow-up of at least 2 years exceeds 40 mo, despite early integration of TARE in a third of the pts within the first 12 mo of diagnosis. Evaluation of pts with CRLM for TARE at experienced centers with dedicated MTB might lead to improved outcomes. [Table: see text]